BACKGROUND Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes. OBJECTIVE AND RATIONALE We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection. SEARCH METHODS Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2. OUTCOMES We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women). WIDER IMPLICATIONS Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.

中文翻译：

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孕妇 COVID-19：关于流产风险和患病率的系统评价和荟萃分析。


背景 感染严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 的孕妇更有可能早产，她们的新生儿更有可能死产或入住新生儿病房。世界卫生组织于 2023 年 5 月宣布结束 2019 冠状病毒病 （COVID-19） 大流行这一全球卫生紧急事件。然而，孕妇仍然会感染 SARS-CoV-2，关于怀孕早期 SARS-CoV-2 感染对妊娠结局影响的可用信息有限。客观和基本原理 我们进行了本系统综述，以确定 SARS-Cov-2 感染女性早期妊娠丢失的患病率，并将风险与未感染 SARS-CoV-2 的孕妇进行比较。检索方法 我们的系统评价基于前瞻性注册方案。PregCov19 联盟的搜索补充了额外的电子搜索，专门针对截至 2023 年 3 月 10 日在 PubMed、Google Scholar 和 LitCovid 中感染 SARS-CoV-2 的孕妇的流产。我们纳入了对感染 SARS-CoV-2 的孕妇的回顾性和前瞻性研究，前提是它们包含妊娠早期和/或妊娠中期流产的信息。主要结局是流产定义为妊娠 20 周前的流产，然而，也纳入了报告 22 或 24 周内流产的研究。此外，我们报告了将流产定义为发生在妊娠早期和/或孕中期的研究，但没有具体说明胎龄，并且仅当研究将死产和/或胎儿流产与流产分开时，才报告了孕中期流产。数据分为妊娠早期和妊娠中期。 次要结局是异位妊娠 （任何宫外妊娠） 和终止妊娠。至少有 3 名研究人员独立提取资料并评估研究质量。我们计算了比值比 （OR） 和风险差 （RDs） 以及相应的 95% CI，并使用随机效应荟萃分析合并数据。为了估计风险患病率，我们对比例进行了meta分析。通过 I2 评估异质性。结果： 我们纳入了 120 项研究，共涉及 168 444 名感染 SARS-CoV-2 的孕妇;其中 18 233 名妇女处于妊娠早期或中期。证据水平被认为具有低到中等质量，主要是由于选择偏倚。我们没有发现 SARS-CoV-2 感染与流产之间存在关联的证据 （OR 1.10,95% CI 0.81-1.48;I2 = 0.0%;RD 0.0012,95% CI -0.0103 至 0.0127;I2 = 0%;9项研究，4439名女性）。流产率为 9.9% （95% CI 6.2-14.0%;I2 = 68%;46 项研究，1797 名女性）在妊娠早期感染 SARS CoV-2 的女性和 1.2% （95% CI 0.3-2.4%;I2 = 34%;33 项研究;3159 名女性）。SARS-CoV-2 感染女性异位妊娠的比例为 1.4% （95% CI 0.02-4.2%;I2 = 66%;14项研究，950名女性）。终止妊娠发生在 0.6% 的妇女中 （95% CI 0.01-1.6%;I2 = 79%;39 项研究;1166 名女性）。更广泛的影响 我们的研究发现，没有迹象表明妊娠早期或中期感染 SARS-CoV-2 会增加流产的风险。 为了提供更好的风险估计，需要设计良好的研究，包括受孕和怀孕早期感染和未感染 SARS-CoV-2 的孕妇，并考虑 SARS-CoV-2 感染的临床表现和严重程度与流产的关联，以及潜在的混杂因素，例如既往流产。在临床实践中，仍应建议孕妇采取预防措施，以避免接触 SARS-CoV-2 的风险并接种 SARS-CoV-2 疫苗。